EP 1378512 A1 20040107 - Optically pure camptothecin analogues

Title (en)

Optically pure camptothecin analogues

Title (de)

Optisch reine Camptothecinanaloge

Title (fr)

Analogues optiquement purs de la camptothécine

Publication

EP 1378512 A1 20040107 (FR)

Application

EP 03077049 A 19980807

Priority

EP 98941567 A 19980807
FR 9710785 A 19970829

Abstract (en)

Two optically pure beta-hydroxy lactone camptothecin analogs (+)-5-ethyl-9,10-difluoro-5-hydroxy-4,5,13,15-tetrahydro-1H,3H-oxepino(3',4':6,7)indolizino(1,2-b)quinoline-3,15-dione (I) and (+)-9-chloro-5-ethyl-5-hydroxy-10-methyl-12-(4-methylpiperidinomethyl)-4,5,13,15-tetrahydro-1H,3H-oxepino(3',4':6,7)indolizino(1,2-c)quinoline-2,15-dione (II), as well as one of its salts, (+)-1-(9-chloro-5-ethyl-5-hydroxy-10-methyl-3,15-dioxo-4,5,13,15-tetrahydro-1H,3H-oxepino(3',4':6,7)indolizino(1,2-b)quinoline-12-yl methyl)-4-methyl-hexahydropyridinium chloride (III) and intermediates (M) are new. Optically pure beta-hydroxy lactone camptothecin analogs of formulae (I) and (II), as well as salts of (II) of formulae (III) are new. Independent claims are also included for industrial intermediates of formula (M) and their preparation. R = 1-10C alkyl, especially ethyl.

Abstract (fr)

L'invention concerne de nouveaux analogues de la camptothécine et en particulier les produits répondant aux formules suivantes : (+)-5-éthyl-9,10-difluoro-5-hydroxy-4,5,13,15-tétrahydro-1H, 3H-oxépino[3',4':6,7]indolizino[1,2-b]quinoline-3,15-dione ; (+)-chlorure de 1-[9-chloro-5-éthyl-5-hydroxy-10-méthyl-3,15-dioxo-4,5,13,15-tétrahydo-1H, 3H-oxépino[3',4':6,7]indolizino[1,2-b]quinolin-12-ylméthyl]-4-méthyl-hexahydropyridinium ; leur application comme médicaments, les compositions pharmaceutiques les renfermant et leur utilisation pour la réalisation de médicaments antitumoraux, antiviraux ou antiparasitaires. Elle concerne également un nouvel intermédiaire dans la synthèse des produits susmentionnés ainsi qu'un procédé de préparation dudit intermédiaire.

IPC 1-7

C07D 491/04; C07D 491/22; A61K 31/435

IPC 8 full level

A61K 31/435 (2006.01); A61K 31/4353 (2006.01); A61K 31/4375 (2006.01); C07D 491/22 (2006.01); A61P 31/12 (2006.01); A61P 33/00 (2006.01); A61P 35/00 (2006.01); C07D 491/04 (2006.01); C07D 491/044 (2006.01)

CPC (source: EP KR)

A61P 31/12 (2018.01 - EP); A61P 33/00 (2018.01 - EP); A61P 35/00 (2018.01 - EP); C07D 491/04 (2013.01 - EP); C07D 491/22 (2013.01 - KR)

Citation (search report)

[XD] WO 9700876 A1 19970109 - SOD CONSEILS RECH APPLIC [FR], et al
[A] US 5459269 A 19951017 - COMINS DANIEL L [US]

Designated contracting state (EPC)

AT BE CH CY DE DK ES FI FR GB GR IE IT LI LU MC NL PT SE

DOCDB simple family (publication)

WO 9911646 A1 19990311; AR 016856 A1 20010801; AT E253069 T1 20031115; AU 760863 B2 20030522; AU 8989698 A 19990322; BR 9811405 A 20000829; CA 2301739 A1 19990311; CA 2301739 C 20091117; CN 1104434 C 20030402; CN 1195758 C 20050406; CN 1268948 A 20001004; CN 1440972 A 20030910; CN 1440973 A 20030910; CZ 2000711 A3 20000816; CZ 297896 B6 20070425; DE 69819340 D1 20031204; DE 69819340 T2 20040819; DK 1007527 T3 20040308; EP 1007527 A1 20000614; EP 1007527 B1 20031029; EP 1378512 A1 20040107; ES 2209196 T3 20040616; FR 2768431 A1 19990319; FR 2768431 B1 20000324; HK 1031732 A1 20010622; HK 1058665 A1 20040528; HR P20000110 A2 20010228; HU P0003429 A1 20010730; HU P0003429 A3 20021128; IL 134437 A0 20010430; IL 134437 A 20060801; JP 2001514261 A 20010911; KR 100570254 B1 20060412; KR 20010023394 A 20010326; NO 20000995 D0 20000228; NO 20000995 L 20000228; NO 324882 B1 20071227; NZ 502862 A 20021025; PL 195289 B1 20070831; PL 338835 A1 20001120; PT 1007527 E 20040331; RU 2233283 C2 20040727; TW 419479 B 20010121; ZA 987445 B 19990217

DOCDB simple family (application)

FR 9801768 W 19980807; AR P980104157 A 19980821; AT 98941567 T 19980807; AU 8989698 A 19980807; BR 9811405 A 19980807; CA 2301739 A 19980807; CN 03102165 A 20030208; CN 03102166 A 19980807; CN 98808720 A 19980807; CZ 2000711 A 19980807; DE 69819340 T 19980807; DK 98941567 T 19980807; EP 03077049 A 19980807; EP 98941567 A 19980807; ES 98941567 T 19980807; FR 9710785 A 19970829; HK 01102373 A 20010403; HK 04101371 A 20040225; HR P20000110 A 20000229; HU P0003429 A 19980807; IL 13443700 A 20000208; IL 13443798 A 19980807; JP 2000508685 A 19980807; KR 20007002034 A 20000228; NO 20000995 A 20000228; NZ 50286298 A 19980807; PL 33883598 A 19980807; PT 98941567 T 19980807; RU 2000107822 A 19980807; TW 87113646 A 19980819; ZA 987445 A 19980818